Cell models are instrumental for studying basic and applied aspects of gene and molecular therapy for cystic fibrosis (CF). Human airway epithelial cell cultures maintained at an air-liquid interface and displaying mucociliary differentiation similar to the in vivo epithelium faithfully reproduce high resistance to gene therapy vectors characteristic of the native human mucosa. There cultures facilitate understanding vector interaction with target cells and provide a strong platform for pre-clinical studies vital to the success of gene and molecular therapy for CF. A Tissue Procurement and Cell Culture Core was established at the University of North Carolina (UNC) in 1984, under the auspices of the CF Foundation, to provide standardized cell cultures to CF researchers. The Core has supported UNC Gene Therapy for CF projects since 1993 and has increased its output and capabilities to meet growing research demands. The Core routinely makes available cells and media that are unavailable and/or prohibitively expensive if purchased from commercial suppliers. The Core has focused on providing human airway epithelial cell cultures to UNC CF Center investigators. The present application will support continuing essential services and will increase the range of services to the University -wide gene and molecular therapy community. The Core provides human airway epithelial cells in environments more representative of in vivo conditions, supports relevant in vivo models and supplies additional cell types including progenitor cells. To accomplish these goals, we propose the following specific aims; 1) to provide normal and CF human and mouse airway epithelial cells in model systems reproducing important elements of the in vivo airway environment, 2) to cost effectively provide additional lung cell types that are high priority targets for the UNC gene and molecular therapy community, and 3) to cost effectively provide liver and intestine cell types under investigation by the UNC gene and molecular community. Through these functions, and in conjunction with the other Cores in this application, the Cell Models Core will foster collaborations directed at improving vector efficiency to both the airway epithelium and additional cell and organ systems relevant to the research mission of NIDDK.